Emerging Pharmacological Therapeutic Agents for Tinnitus Publisher



Zonnour A ; Abouzari M ; Djalilian HR
Source: Published:2025

Abstract

Tinnitus, the perception of sound without external stimuli, is a significant health burden globally. Effective treatment remains elusive due to an incomplete understanding of its mechanisms, heterogeneous manifestations, and limited treatment options. Current pharmacological options for acute tinnitus treatment follow sudden hearing loss guidelines, recommending systemic or intratympanic steroids. Existing medications for chronic tinnitus mostly focus on alleviating the intensity of symptoms including tricyclic antidepressants, benzodiazepines, and lidocaine, showing varied efficacy and safety. However, various guidelines recommend against currently available pharmacological interventions due to insufficient efficacy and potential side effects. Ongoing studies on emerging pharmacological treatments target various pathways to treat tinnitus effectively. Migraine treatments address the migraine-tinnitus link, offering relief by targeting underlying migraine pathology. Inflammatory pathways represent another promising target, with TNF-α inhibitors showing promise in animal models. Potassium channel modulators, such as Kv3 K+ channel activators and BK channel openers, are being investigated for their potential in modulating neuronal hyperexcitability and administrating agents targeting those demonstrated promising results in animal studies. GABAergic drugs, including extrasynaptic GABAA receptor modulators, offer a strategy to reduce abnormal hyperactivity which needs further investigations. Glutamate receptor antagonists, like mGluR agonists and AMPA receptor antagonists, hold promise in suppressing tinnitus in animal models. Also, potential treatment targets such as the limbic system, lipid metabolism, and synaptic genes have gained interest in recent studies. Moreover, ongoing clinical trials investigate novel treatment options like migraine medications, Etanercept, Brexanolone, and Curcumin for tinnitus management. Challenges include methodological flaws in trials, lack of standardization across studies, tinnitus heterogeneity, and limited pharmacological options. Overcoming these requires standardized criteria, longer follow-ups, and diversified trial designs. Despite challenges, advancements in neuroinflammation and genetics and brain-targeted interventions offer promising drug targets. Lastly, establishing personalized treatment approaches will be crucial for improving tinnitus care and outcomes. © 2025 Elsevier B.V., All rights reserved.